Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders
Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders
复制标题
DOI：
10.1182/blood-2005-11-009605
复制
发表时间：
2006-08-15
期刊：
影响因子：
20.3
通讯作者：
Skoda, Radek G.
中科院分区：
文献类型：
--
作者：
Kralovics, Robert;Teo, Soon-Siong;Skoda, Radek G.
在骨髓增生性疾病(MPDS)患者中经常发现Janus激酶2(JAK2V617F)的获得性功能获得突变。为了验证JAK2-V617F是致病突变的假设，我们检查了是否所有克隆起源的细胞都携带JAK2-V617F突变。用等位基因特异性聚合酶链式反应(PCR)检测JAK2突变和X染色体克隆性标志物IDs和MPP1，我们发现在女性患者中，JAK2V617F携带者的粒细胞和血小板比例往往明显低于IDS法或MPP1克隆法测定的克隆性粒细胞百分比。使用染色体20q缺失(De120q)作为常染色体、X染色体非依赖性克隆性标记，我们发现携带JAK2-V617F的细胞百分比与de120q相似。我们的结果表明，在一定比例的MPDS患者中，JAK2-V617F发生在一个未知基因的体细胞突变引起的克隆性造血的背景下。
An acquired gain-of-function mutation in the Janus kinase 2 (JAK2V617F) is frequently found in patients with myeloproliferative disorders (MPDs). To test the hypothesis that JAK2-V617F is the disease-initiating mutation, we examined whether all cells of clonal origin carry the JAK2-V617F mutation. Using allele-specific polymerase chain reaction (PCR) assays for the JAK2 mutation and for the X-chromosomal clonality markers IDS and MPP1, we found that the percentage of granulocytes and platelets with JAK2V617F was often markedly lower than the percentage of clonal granulocytes determined by IDS or MPP1 clonality assays in female patients. Using deletions of chromosome 20q (de120q) as an autosomal, X-chromosome-independent clonality marker, we found a similar discrepancy between the percentage of cells carrying JAK2-V617F and de120q. Our results suggest that in a proportion of patients with MPDs, JAK2-V617F occurs on the background of clonal hematopoiesis caused by a somatic mutation in an as-yet-unknown gene.